The hosts secured their spot in the third round of the qualifiers by virtue of their 3-1 aggregate victory over Universidad de Chile in the last round.
Franco Di Santo scored a late equalizer to help his side secure a 1-1 draw away in the first leg and was also on the scoresheet in the second leg 2-0 victory.
Santos secured a 3-2 aggregate victory over Venezuelan side Deportivo Lara. A 2-1 victory at home was followed by a 1-1 draw in Caracas.
A place in the group stage awaits the winner of this tie and both sides will be keen to get a positive result in the first leg.
San Lorenzo vs Santos Head-to-Head
The two sides have met on two previous occasions, with one victory recorded apiece.
This came in both legs of the 2006 Copa Sudamericana round of 16, when a 3-0 home victory was registered by San Lorenzo in the first leg. This was followed by a 1-0 win for Santos in the return fixture but the Argentine side progressed to the quarterfinals.
Santos have not been in action since their 1-1 draw with Deportivo Lara in March. The hosts come into this game on the back of consecutive victories in the Argentine league.
San Lorenzo form guide (all competitions): W-W-L-L-W
Santos form guide (all competitions): D-W-W-L-D
San Lorenzo vs Santos Team News
The hosts have two players ruled out with injuries. Yelson Gordillo (foot) and Sebastian Torrico (shoulder) are both unavailable for selection.
There are no suspension worries for San Lorenzo.
Injuries: Sebastian Torrico, Yelson Gordillo
The visitors have four players sidelined through injury. Jobson, Carlos Sanchez and Rafael Longuine have all been sidelined by long-term ACL injuries. Meanwhile, midfielder Raniel has been ruled out with an Achilles tendon issue.
Jonathan Copete has tested positive for COVID-19 and is currently in self-isolation.
There are no suspension concerns for coach Ariel Holan.
Injuries: Jobson, Carlos Sanchez, Longuine, Raniel
COVID-19: Jonathan Copete
San Lorenzo vs Santos Predicted XI
San Lorenzo Predicted XI (4-3-3): Jose Devecchi (GK); Gabriel Rojas, Diego Braghieri, Federico Gattoni, Gino Peruzzi; Oscar Romero, Jalil Elias, Julian Palacios; Angel Romero, Franco Di Santo, Lucas Santiago Melano
Santos Predicted XI (4-2-3-1): John (GK); Felipe Jonathan, Luan Peres, Kaiky Fernandes, Vinicius Balieiro; Sandry Roberto, Gabriel Pirani; Marcos Leonardo, Lucas Braga, Angelo Gabriel; Jean Mota
San Lorenzo vs Santos Prediction
The fact that San Lorenzo have been in action for the last few months compared to Santos, who have been inactive, gives the hosts a massive edge.
The Brazilians would typically have enough quality and pedigree to overcome this challenge. However, we are predicting a narrow victory for San Lorenzo in this instance.
Prediction: San Lorenzo 2-0 Santos